2. NOMAD:2005: BP: INTROVERVIEW 1 THE PHYSIOLOGY OF BLOOD AN INTRODUCTION AND OVERVIEW By Dr.M.ANTHONY DAVID, MD.

3. NOMAD:2005: BP: INTROVERVIEW 2 WHAT IS BLOOD ? IT IS A LIQUID CONNECTIVE TISSUE IT IS A LIQUID CONNECTIVE TISSUE IN AN AVERAGE 70 Kg MAN: IN AN AVERAGE 70 Kg MAN: 100 Trillion cells. 100 Trillion cells. Of which 25 trillions are Red Blood Cells! Of which 25 trillions are Red Blood Cells! The average blood volume is 5 – 6 lts. The average blood volume is 5 – 6 lts. It is roughly 7% of the total body weight. It is roughly 7% of the total body weight.

4. NOMAD:2005: BP: INTROVERVIEW 3 HEMATOLOGY: THE STUDY OF BLOOD MADE POSSIBLE BY MICROSCOPY

5. NOMAD:2005: BP: INTROVERVIEW 4 THE COMPOSITION OF BLOOD PLASMA The Liquid: Plasma: The Liquid: Plasma: Water, the solvent Water, the solvent The solute: The solute: Proteins: Proteins: Albumin Albumin Globulins:# Globulins:# Fibrinogen Fibrinogen Electrolytes: Electrolytes: Na+ Na+ K+ K+ Ca++ Ca++ Organic molecules Organic molecules Urea Urea Glucose Glucose Lipids Lipids BLOOD PLASMA WATERSOLUTES PROTEINS ELECTRO -LYTES ORGANIC MOLECULES

6. NOMAD:2005: BP: INTROVERVIEW 5 THE FORMED ELEMENT: CELLS BLOOD CELLS ERYTHROCYTESLEUCOCYTESTHROMBOCYTES

7. NOMAD:2005: BP: INTROVERVIEW 6 BLOOD: COMPOSITION

8. NOMAD:2005: BP: INTROVERVIEW 7 FUNCTIONS OF BLOOD NUTRITIVE RESPIRATORY EXCRETORY BODY DEFENCE: IMMUNITY TRANSPORT: HORMONES VITAMINS DRUGS

9. NOMAD:2005: BP: INTROVERVIEW 8 BLOOD:TRANSPORTING HORMONE MOLECULES

10. NOMAD:2005: BP: INTROVERVIEW 9 OXYGEN & CO 2 TRANSPORT

11. NOMAD:2005: BP: INTROVERVIEW 10 FUNCTIONS OF BLOOD HOMEOSTATIC FUNCTION: HOMEOSTATIC FUNCTION: ACID BASE BALANCE. ACID BASE BALANCE. ELECTROLYTE BALANCE. ELECTROLYTE BALANCE. HEMOSTASIS. HEMOSTASIS. THERMOREGULATION. THERMOREGULATION.

12. NOMAD:2005: BP: INTROVERVIEW 11 WHAT IS BLOOD VOLUME? The total amount of blood in circulation plus the amount of blood in the reservoirs constitutes the “Blood Volume” The total amount of blood in circulation plus the amount of blood in the reservoirs constitutes the “Blood Volume” The average adult 70 kg man has a blood volume of 5 to 6 litres. The average adult 70 kg man has a blood volume of 5 to 6 litres.

13. NOMAD:2005: BP: INTROVERVIEW 12 EXPRESSION OF BLOOD VOLUME Usually Blood Volume is expressed in liters. Usually Blood Volume is expressed in liters. It can also be expressed in relation to body weight. It can also be expressed in relation to body weight. It is 7% Body Weight It is 7% Body Weight Another way to express it is in terms of Body Surface Area. Another way to express it is in terms of Body Surface Area. Whole Blood : 2.8 Lts/M 2 Whole Blood : 2.8 Lts/M 2 Plasma : 1.5 Lts/M 2 Plasma : 1.5 Lts/M 2

14. NOMAD:2005: BP: INTROVERVIEW 13 IN HUMANS: ONLY INDIRECT METHODS IN HUMANS: ONLY INDIRECT METHODS DYE DILUTION TECHNIQUE: DYE DILUTION TECHNIQUE: PRINCIPLE: PRINCIPLE: Injection of a known volume of non toxic substance into the circulation. Injection of a known volume of non toxic substance into the circulation. Measuring the dilution of this injected dye after some time. Measuring the dilution of this injected dye after some time. This gives us the Plasma volume. This gives us the Plasma volume. METHODS OF MEASURING BLOOD VOLUME

15. NOMAD:2005: BP: INTROVERVIEW 14 DYE DILUTION TECHNIQUE V 1 = VOLUME C 1 = CONCENTRATION OF DYE V 2 = VOLUME C 2 = CONC. OF DYE V 1 X C 1 = V 2 X C 2 OR V 2 = V 1 X C 1 = Amount of Dye injected C 2 Conc. Of the dye in the Plasma

16. NOMAD:2005: BP: INTROVERVIEW 15 HEMATOCRIT (PCV) The volume of erythrocytes in the whole blood expressed in percentage is the Hematocrit. The volume of erythrocytes in the whole blood expressed in percentage is the Hematocrit. This is also called as Packed Cell Volume or PCV. This is also called as Packed Cell Volume or PCV. This is determined by the Wintrobe’s tube, using a Centrifuge. This is determined by the Wintrobe’s tube, using a Centrifuge.

17. NOMAD:2005: BP: INTROVERVIEW 16 HEMATOCRIT A mixture of blood and double oxalate (K – NH 4 ) is taken upto 100 mark in the Wintrobe’s tube. A mixture of blood and double oxalate (K – NH 4 ) is taken upto 100 mark in the Wintrobe’s tube. The tube is placed in the centrifuge. The tube is placed in the centrifuge. It is rotated at 3,000 rpm for 30 minutes. It is rotated at 3,000 rpm for 30 minutes. The Hematocrit is then read off the tube. The Hematocrit is then read off the tube. Blood Volume = Plasma Volume X 100 Blood Volume = Plasma Volume X 100 100 - PCV

18. NOMAD:2005: BP: INTROVERVIEW 17 HEMATOCRIT

19. NOMAD:2005: BP: INTROVERVIEW 18 BLOOD VOLUME: PHYSIOLOGICAL VARIATIONS AGE AGE SEX SEX TEMPERATURE TEMPERATURE BODY WEIGHT BODY WEIGHT BODY SURFACE AREA BODY SURFACE AREA PREGNANCY PREGNANCY EXERCISE EXERCISE POSTURE POSTURE HYPOXIA HYPOXIA EMOTIONS EMOTIONS

20. NOMAD:2005: BP: INTROVERVIEW 19 BLOOD VOLUME & AGE AGE BLOOD VOLUME in Liters AT BIRTH 0.3 6 Months 0.5 1 year 0.7 2yrs 6 months 1.0 4 years 1.3 7 years 1.7 10 years 2.5(Girls); 3.2 (Boys) ADULTS 5 (Men) 4.5 (Women)

21. NOMAD:2005: BP: INTROVERVIEW 20 BLOOD VOLUME: PHYSIOLOGICAL VARIATIONS 1. SEX: Males have more blood volume than females. Males have more blood volume than females. 2. TEMPERATURE: Acute exposure to cold causes reduction in blood volume due to Plasma water loss to tissues. Acute exposure to cold causes reduction in blood volume due to Plasma water loss to tissues.

22. NOMAD:2005: BP: INTROVERVIEW 21 3. BODY WEIGHT: It is usually 7% of the Body Weight. 4. BODY SURFACE AREA: 2.8 Lts/Square Meters of BSA BLOOD VOLUME: PHYSIOLOGICAL VARIATIONS

23. NOMAD:2005: BP: INTROVERVIEW 22 5. PREGNANCY: Increases by 20 – 30% due to mass of fetus. Increases by 20 – 30% due to mass of fetus. 6. EXERCISE: Vigorous exercise causes an increase. Vigorous exercise causes an increase. 7. POSTURE: Changing from lying down to erect. Changing from lying down to erect. BLOOD VOLUME: PHYSIOLOGICAL VARIATIONS

24. NOMAD:2005: BP: INTROVERVIEW 23 BLOOD VOLUME: PHYSIOLOGICAL VARIATIONS 8. HYPOXIA: Seen in High altitudes.  Erythrocytes So  Blood volume. 9. EMOTIONS: Excitement causes an increase in the Blood volume.

25. NOMAD:2005: BP: INTROVERVIEW 24 BLOOD VOLUME: PATHOLOGICAL VARIATIONS DECREASE IN BLOOD VOLUME IS HYPOVOLEMIA. CAUSES: DECREASE IN BLOOD VOLUME IS HYPOVOLEMIA. CAUSES: 1. BLOOD LOSS: 2. SHOCK: 2. SHOCK: Crushing Injury Crushing Injury Cardiogenic Cardiogenic Neurogenic Neurogenic Psychogenic. Psychogenic.

26. NOMAD:2005: BP: INTROVERVIEW 25 3. HEMOLYSIS: Mismatched transfusion Snake bite Black water fever Hemorrhagic Plagues/Dengue Measles HYPOVOLEMIA: CAUSES (contd)

27. NOMAD:2005: BP: INTROVERVIEW 26 4. DEHYDRATION: Diarrhoea Diarrhoea Cholera Cholera Gastroenteritis Gastroenteritis Burns Burns Hyperemesis. Hyperemesis. HYPOVOLEMIA: CAUSES (contd)

28. NOMAD:2005: BP: INTROVERVIEW 27 5. ANEMIA: Decreased RBC volume Decreased RBC volume Plasma may increase. Plasma may increase. 6. OBESITY: Blood volume per body weight decreases though Blood volume per BSA may be normal. Blood volume per body weight decreases though Blood volume per BSA may be normal. 7. HYPOTHYROIDISM (MYXEDEMA): Decrease in Blood volume. Decrease in Blood volume. 8. ACUTE COLD: Decreases blood volume. HYPOVOLEMIA: CAUSES (contd)

29. NOMAD:2005: BP: INTROVERVIEW 28 TREATMENT FOR BLOOD LOSS TRANSFUSION OF WHOLE BLOOD OF THE SAME BLOOD GROUP & TYPE. TRANSFUSION OF WHOLE BLOOD OF THE SAME BLOOD GROUP & TYPE. INFUSION OF PLASMA INFUSION OF PLASMA INFUSION OF DEXTRAN OR NORMAL SALINE. INFUSION OF DEXTRAN OR NORMAL SALINE.

30. NOMAD:2005: BP: INTROVERVIEW 29 HEMOPOIESIS & ERYTHROPOIESIS By Dr. M.Anthony David.MD.

31. NOMAD:2005: BP: INTROVERVIEW 30 HEMOPOIESIS: INTRO Hemo: Referring to blood cells Poiesis: “The development or production of” The word Hemopoiesis refers to the production & development of all the blood cells: Erythrocytes: Erythropoiesis Leucocytes: Leucopoiesis Thrombocytes: Thrombopoiesis. Begins in the 20 th week of life in the fetus & continues in the red bone marrow till death.

32. NOMAD:2005: BP: INTROVERVIEW 31 STEM CELL THEORY All blood cells are produced by the bone marrow. All blood cells are produced by the bone marrow. They come from a single class of primitive mother cells called as: They come from a single class of primitive mother cells called as: PLURIPOTENT STEM CELLS. PLURIPOTENT STEM CELLS. These cells give rise to blood cells of: These cells give rise to blood cells of: Myeloid series: Cells arising mainly from the bone marrow. Myeloid series: Cells arising mainly from the bone marrow. Lymphoid series: cells arising from lymphoid tissues. Lymphoid series: cells arising from lymphoid tissues.

33. NOMAD:2005: BP: INTROVERVIEW 32 PROGENITOR CELLS Committed stem cells lose their capacity for self-renewal. Committed stem cells lose their capacity for self-renewal. They become irreversibly committed. They become irreversibly committed. These cells are termed as “Progenitor cells” These cells are termed as “Progenitor cells” They are regulated by certain hormones or substances so that they can: They are regulated by certain hormones or substances so that they can: Proliferate Proliferate Undergo Maturation. Undergo Maturation.

34. NOMAD:2005: BP: INTROVERVIEW 33 BLOOD CELLS: DEVELOPMENT PROGENITOR CELLS LYMPHOID CELLS LYMPHOCYTES PRO NORMOBLAST ERYTHROCYTES MEGA KARYOBLAST THROMBOCYTES MYELOBLAST GRANULOCYTES MONOBLAST MONOCYTES

35. NOMAD:2005: BP: INTROVERVIEW 34 ERYTHROPOIESIS: SITES/PHASES INTRAUTERINE LIFE: INTRAUTERINE LIFE: INTRAVASCULAR PHASE: Upto 3 rd month of Intra Uterine Life. INTRAVASCULAR PHASE: Upto 3 rd month of Intra Uterine Life. Endothelial cells = = = RBCs Endothelial cells = = = RBCs HEPATIC PHASE: 3 rd to 5 th month IUL HEPATIC PHASE: 3 rd to 5 th month IUL Liver & Spleen Liver & Spleen nRBCs from Mesenchymal cells. nRBCs from Mesenchymal cells. MYELOID PHASE: From 5 th month of IUL onwards. MYELOID PHASE: From 5 th month of IUL onwards.

36. NOMAD:2005: BP: INTROVERVIEW 35 POST NATAL LIFE: POST NATAL LIFE: CHILDREN: CHILDREN: Predominantly Red Bone Marrow of skeleton: Predominantly Red Bone Marrow of skeleton: Axial & Axial & Appendicular. Appendicular. ADULTS: ADULTS: Red Bone Marrow of Axial Skeleton. Red Bone Marrow of Axial Skeleton. ERYTHROPOIESIS: SITES/PHASES contd.

37. NOMAD:2005: BP: INTROVERVIEW 36 ERYTHROPOIESIS

38. NOMAD:2005: BP: INTROVERVIEW 37 FACTORS REGULATING ERYTHROPOIESIS SINGLE MOST IMPORTANT REGULATOR: “TISSUE OXYGENATION” SINGLE MOST IMPORTANT REGULATOR: “TISSUE OXYGENATION” BURST PROMOTING ACTIVITY BURST PROMOTING ACTIVITY ERYTHROPOIETIN ERYTHROPOIETIN IRON IRON VITAMINS: VITAMINS: Vitamin B 12 Vitamin B 12 Folic Acid Folic Acid MISCELLANEOUS MISCELLANEOUS

39. NOMAD:2005: BP: INTROVERVIEW 38 ERYTHROPOIETIN A hormone produced by the Kidney. A hormone produced by the Kidney. Nowadays available as Synthetic Epoieti Nowadays available as Synthetic Epoieti Increases the number of: Increases the number of: Nucleated precursors in the marrow. Nucleated precursors in the marrow. Reticulocytes & Mature Erythrocytes in the blood. Reticulocytes & Mature Erythrocytes in the blood.

40. NOMAD:2005: BP: INTROVERVIEW 39 VITAMINS B 12 : Cyanocobalamine & Folic Acid: B 12 : Cyanocobalamine & Folic Acid: Is also called Extrinsic Factor of Castle. Is also called Extrinsic Factor of Castle. Needs the Intrinsic Factor from the Gastric juice for absorption from Small Intestine. Needs the Intrinsic Factor from the Gastric juice for absorption from Small Intestine. Deficiency causes Pernicious (When IF is missing) or Megaloblastic Anemia. Deficiency causes Pernicious (When IF is missing) or Megaloblastic Anemia. Stimulates Erythropoiesis Stimulates Erythropoiesis Is found in meat & diary products. Is found in meat & diary products.

41. NOMAD:2005: BP: INTROVERVIEW 40 IRON Essential for the synthesis of Hemoglobin. Essential for the synthesis of Hemoglobin. Deficiency causes Microcytic, Hypochromic Anemia. Deficiency causes Microcytic, Hypochromic Anemia. Deficiency causes the commonest type of Anemia. Deficiency causes the commonest type of Anemia.

42. NOMAD:2005: BP: INTROVERVIEW 41